Inflammatory and Antioxidant Gene Transcripts: A Novel Profile in Postoperative Atrial Fibrillation.

Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery; however, antiarrhythmic strategies have not lowered the rate of POAF. This study aimed to identify specific gene transcripts of atrial inflammation, inflammatory handling, and oxidative stress associated with POAF. Left atrial tissue was obtained from 50 patients undergoing intended degenerative mitral repair who did not have any of the following risk factors for POAF: history of atrial fibrillation or other arrhythmia, left atrial diameter greater than 6.0 cm, or left ventricular ejection fraction less than 40%. Postoperative outcomes and left atrial tissue messenger ribonucleuc acid (mRNA) levels were recorded. Parametric 2-sample t-tests and chi-square tests were used to evaluate for statistical significance in comparing POAF and non-POAF groups. Within 30 days of surgery, 19 of 50 of patients (38%) developed POAF. There were no significant preoperative, intraoperative, or postoperative differences between POAF and non-POAF patients. In the tissue transcriptome analysis, POAF patients were found to have a worse preoperative inflammatory state with higher levels of tumor necrosis factor alpha, Interleukin-6, and nuclear factor of kappa light polypeptide gene enhancer in B-cells mRNA, worse inflammatory handling capacity with lower levels of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor mRNA, and reduced antioxidant defenses with lower levels of glutathione synthetase, glutathione reductase, and mitochondrial superoxide dismutase 2 mRNA. This study found POAF patients to have preoperative left atrial tissue profiles suggestive of more inflammation, worse inflammatory handling, and reduced antioxidant defenses against oxidative stress. Investigation of therapies targeted to the tissue-specific inflammatory transcriptome of POAF patients is warranted.

Anticoagulation following mitral valve repair.

BACKGROUND AND AIM: Anticoagulation after mitral valve repair is controversial and guidelines are not well-established. This study evaluated the association between postoperative warfarin use and complications after mitral valve repair, including bleeding and thromboembolic incidents, readmission, and mortality. METHODS: This retrospective study investigated 1097 patients who underwent elective mitral valve repair between April 2003 and March 2017, and was naïve to atrial fibrillation or prior cardiac surgery. This cohort had no other indication for or against anticoagulation. About 775 patients were placed on warfarin with international normalized ratio goal 2.5 and 322 patients were not anticoagulated. The association between anticoagulation and complications was assessed with univariate comparisons between groups and multiple logistic regression. RESULTS: Postoperative warfarin use was associated with a reduced composite of bleeding and thromboembolic complications (pulmonary embolism, TIA, stroke, pericardial effusion or cardiac tamponade, gastrointestinal bleeding, and reoperation for bleeding) with an odds ratio of 0.29 (95% confidence interval, 0.13-0.64, P = .003). There was no difference in 30-day or 6-month mortality or readmission rate between groups. Long-term survival estimates were superior in the warfarin group (10-year: 92% vs 85%; log-rank P < .001). CONCLUSIONS: Our analysis showed that postoperative warfarin use was associated with an overall reduced composite of bleeding and thromboembolic incidents and superior long-term survival. These findings suggest that anticoagulation with warfarin following mitral valve repair may be a safe and effective means for avoiding postoperative complications and that a large prospective randomized clinical trial is warranted.

MDI 301 suppresses myeloid leukemia cell growth in vitro and in vivo without the toxicity associated with all-trans retinoic acid therapy.

MDI 301 is a novel 9-cis retinoic acid derivative in which the terminal carboxylic acid group has been replaced by a picolinate ester. MDI 301, a retinoic acid receptor-α - agonist, suppressed the growth of several human myeloid leukemia cell lines (HL60, NB4, OCI-M2, and K562) in vitro and induced cell-substrate adhesion in conjunction with upregulation of CD11b. Tumor growth in HL60-injected athymic nude mice was reduced. In vitro, MDI 301 was comparable to all-trans retinoic acid (ATRA) whereas in vivo, MDI 301 was slightly more efficacious than ATRA. Most importantly, unlike what was found with ATRA treatment, MDI 301 did not induce a cytokine response in the treated animals and the severe inflammatory changes and systemic toxicity seen with ATRA did not occur. A retinoid with these characteristics might be valuable in the treatment of promyelocytic leukemia, or, perhaps, other forms of myeloid leukemia.